Sleep disorders in psychiatry

György Purebl MD PhD

Sleep = passivity

Sleep = rest

Sleep= tranquillity

Acitve and intensive biological process

Different processes with different functions

Sleep is vital

Sleep-phase functions

NREM-LHA

Developmen Rekonstruction Energy restoration

(ATP) Immune regulation Memory-consolidation

REM

Memory-consolidation and learning

Pszichological well-being

Affective learning Motivation Coping with stress Mood regulation

Siegel Science (2001) 294: 5544

Disturbed sleep leads to psychological and physiological dysfunctions

► Impaired mood regulation

► Increased strerss-alertness

5H1A attenuation

Impaired hippocampal neurogenesis

Severe psychopathological symptoms

Insulin resistence

Impaired immunological fitness

Increased cortizol-level Disturbed GH secretion

Metabolic crisis, death

New bunch of disorders in the XXth Century

ObesityLipid and cholesterol problemsType 2 diabetes

CHD

DepressionAnxiety and stress-related disorders Insomnia and circadian rhytm

disorders

Insomnia amongst top 10 health complaint in XX. Century WHO

Collaborative Survey at Primary Care Level (Ustun es Sartorius 1995)

Turkey

GreeceBANGALORE

Germany

UKJapan

France

Brasil

USAChina

ItalyThe Netherl

0

10

20

30

40

27

20 20

28 28

8

27

40

20 20 19

30

%

Does the relationship of humans to time change?

► Life expectations increasing

► Somatic development accelerates

► Psychosocial development slows down

► Duration of marriages increased(?)

►Changing in chronobiological rhythms:

►Rhythm and timing of reproduction

►Annual rhythms (?)

No change in

► Chronotype

► Circadian rhythm

► Ultradian rhythms (pl. sleep-wake cycle, sleep architect)

Sleep, circadian rhythms and biological clocks

Daily oscillation of metabolic, physiological processes and behaviour

Thermoregulation independent

Under genetic controll, but

Timed by environmental stimuli (zeitgebers) SCN as „master clock”

Circadian rhythm

► Little more than 24 hrs (individual differences!)

► Geneticly encoded (CLOCK, Bmal, per, cry etc. genes)

► Suprachiazmatic nucleus (SCN) as („master clock”)

Controls many homeostatic processes (sleep, metabolism, activity etc)

► The internal clock is losing késik (more than 24 hrs) therefore needs resynchronisation

Specific stimuli act as resychronizing zeitgebers

Stimuli with non-appropriate timing could disturb the rhythm - desychronisation

Zeitgebers

Light/darkness

Exercise

Social activity

Eating

Cultural effects on the Zeitgebers

Light pollution/shortage of light

„Conquest of night”

► Irregular work Lack of exercise Psychoactives

Sleep disorders

► Insomnia

► Circadian rhythm disorders*

► Sleep and movement related sleep disorders

► Parasomnias► Hypersomnia► Narcolepsia► Etc

Hypersomnia

NarcolepsiaKataplexySeep attacksSleep paralysis hypnagogic hallucinations

Depression

OSAS/UARS

Infections

Etc

Th: stimulants (modafinil)

orexinergic agents

Breathing related sleep disorders

OSAS (Obstructive Sleep Apnea Syndrome)

CSAS

UARS (Upper Airwas Resistence Syndrome)

► Obstruction►Hypoxia►Apnea►Lack of SWS – severe sleep deficit►Sympathetic hyperactivity

Risk factors

► Obesity► Hypertension► Diabetes► Mandible anatomy

► Chr. adenoiditis

Consequences

► Arrythmias► Hypertension► Dementia► Diabetes► Sudden death

Th

Lifestyle

Surgical

CPAP

Movement related sleep disorders

► Restless leg syndrome (RLS)► Th: Dopamin agonists (pergolid,

pramipexol) Pain management agents

(gabapentin, opoids*)

► Periodic Limb Movement Disorder (PLMD) Th:

Dopamin agonists (pergolid, pramipexol)

Muscle-relaxants (clonazepam, baclofen)

Anti-seizure drugs (gabapentin)

Paraszomnias

►Sleepwalking

►Sleep terror

►Nightmare disorder

►REM behaviour disorder – the exception!

► Mainly in childhood frequency decreasing with age► No adverse consequences in most of the cases► Possible genetic background

► Diff. Dg.: Epilepsy!

► Th: sleep pills, chorotherapy, supportive psychotherapy

REM Behaviour Disorder

► Later ages► Frequently violent

behaviour► In REM-phase

► Early sign of degenerative CNS disorders!

► Th: REM supression, underlying condition

Insomnia one of the top health complaint

1/3 of the adult population has transient/chronic sleep complaints

9-10% has chronic insomnia

Frequency increasing with age

Nau és mtsai (2005). In: Carney PR, Berry RB, Geyxer JD (eds): Clinical sleep disorders. Ohayon M. (1996). Sleep. 19:S7–S15 Novak és mtsai (2004). J Psychosom Res. 56(5):527-36.

The insomnia syndrome

Difficulty of falling asleep

Difficulty in the maintance of sleep/early morning awakening

Non restorative sleep

Consecutive daytime consequences

The International Classification of Sleep Disorders. Diagnostic and coding manual. Second Edition. 2005. American Academy of Sleep Medicine. Westchester IL

The severity of insomnia is determined by daily symptoms only

IrritabilityFatiqueLow moodAnxietyMemory/

learning difficulties

Decreased concentration and reaction time

Risk of home/workplace/traffic accidents

The International Classification of Sleep Disorders. Diagnostic and coding manual. Second Edition. 2005. American Academy of Sleep Medicine. Westchester IL

Primary (psychophysiological) or secondary insomnia?

► cc. 50% psychiatric comorbidity

► Cc. 50% other medical comorbidity

► Kb 25% psychophysiological- Irregular lifetstyle, distrubed CR- Stress

Psychiatric comorbidity cause or consequence?

Few psychiatric disorder has no insomnia symptom

Few psychiatric disorder has no insomnia risk factor

► Mood disorders► Anxiety disorders► Delusional/psychotic states► Pszichoactive

abusus/withdrawal► Dementia

► Pharmacological treatment

General medical comorbidities

Difficulty of breathing (ec. COPD, severe asthma bronchiale, etc.)

Arteriosclerosis (CHD, Brain vessel damage, cardiomyopáthy)

Hypertension Diabetes Hepatic diseases Hyper- és hypothyreoidism Autoimmun diseases GERD, peptic/duodenal ulcers Bone-joint diseases (rheumatoid arthitis, etc.) Urological diseases Other

Lifestyle factors

► ►Irregular lifestyle►Psychoactives►Lack of exercise►Daily stress►Sleep related worrys and disfunctional

thinking

► Remove the cause but not the symtom

► The sleep related worry became the dominant insomnia maintaining factor in chronic insomnia

Treatment

►We treat the sleep-wake rhythm, not the sleep only

►Preference on sleep quality (REM, SWS), not the duration of sleep

►Lifestyle changes are crucial – just like in diabetes, cardiovascular disorders etc.

Lifestyle and sleep hygiene counselling

Four target of therapyTreatment of underlying mecial condition (if any)SomaticPsychologicalOther sleep disorder

Non pharmacological treatmentCognitive behaviour

therapyChronotherapies (sleep

restriction, light therapy)

PharmacotherapyGABA-erg (nonBZD) hyperarousalMT-erg (MLT-PR, tasimelteon*) CRZ-typeOrexinerg (almorexant*)Certain antidepressives (off label in Europe)

*phase III.

NIH (2005)NICE (2004/2007)Estilvill et al (2003) Clin Drug Invest 23(6): 351-385.

Lifestyle and sleep hygiene counselling

Regularity

Exercise

Restriction of psychoacive agents

Stimulus-control Coping with stress

Management of underlying medical condition

Somatic

Psychological

Other sleep disorder

Non pharmacological treatment

Cognitive Behaviour Therapy (CBT)

Sleep restriction

Relaxation

Light therapy

Pharmacotherapy

Sould not be the only intervention (never in monotherapy)

The least effective approach in chronic insomnia

Arousal-promoting agents:

Catecholamines,

OrexinesHisztaminAcetylcholin 5HTCRH!

Sleep-promoting agents:

5HTGABA–galaninAdenozinMelatonin

GABA-erg (preferable nonBZD) hyperarousal – zolpidem, zopiclon etc

MT-erg (MLT-PR, tasimelteon*) CRZ type

5HT-ergic (eplivanserin*)

Orexinergic (almorexant*)

Mirtazapin, trazodon, myanserin (off label in Europe)

Avoid

►Barbiturates►Glutehtimid►Clomethiazol►Meprobamat►Antipsychotics►Antihisztamines►Ultra-short acting or long-acting BZD-

s!

Heath Ledger (28) Anne Nicole Smiths (39)

►Diazepam►Alprazolam►Temazepam►Doxilamin►Oxikodin►Hydrocodin

►Diazepam►Clonazepam►Lorazepam►Oxazepam►Difenilhidrazin►Chloralhidrate►Topiramate

All in appropriate dose

(other) circadian rhythm disorder

► Jet lag

► Shift work related

► Advanced or delayed sleep-phase syhdrome

Th: chronoterapies: light/darkness, activity/rest resetting, pharmacotherapy

The significance of sleep are increased in medicine

Sleep quality is a major determinant of health and well-being

Disturbed sleep is a health risk factor (ec. depression, diabetes)

The treatment of sleep complaints is prevention: decrease the somatic/psychological health risk

Inappropriate treatment otherwise may lead to more medical problems